Fungicidal n-polyhaloalkylthiosulfonamidothiophenes

ABSTRACT

Novel thiophenes of the formula   WHEREIN X and Z individually are fluoro, chloro or bromc, Y is hydrogen, fluoro, chloro or bromo, R1 is alkyl or aryl and R2 is polyhaloalkyl, are useful for the prevention or cure of fungal infections, particularly Botrytis cinerea.

United States Patent [19] Edwards June 10, 1975 FUNGICIDAL N-POLYHALOALKYLTHIOSULFONAMIDO- THIOPHENES [75] Inventor: Laroy H. Edwards, Napa, Calif.

[73] Assignee: Chevron Research Company, San

Francisco, Calif.

22 Filed: July 29,1974

21 Appl. No.: 489,310

[52] US. Cl 260/329 S; 424/275 [51] Int. Cl C07d 63/00 [58] Field of Search 260/329 S [56] References Cited OTHER PUBLICATIONS Chrzaszczewska, Chemical Abstracts, Vol. 65 (1966), Pg. l2157e.

Primary ExaminerLeon Zitver Assistant ExaminerA. Siegel Attorney, Agent, or Firm-J. A. Buchanan, Jr.; Dix A. Newell; Raymond Owyang [57] ABSTRACT Novel thiophenes of the formula 10 Claims, No Drawings FUNGICIDAL N -POLYI-IALOALKYLTI-IIOSULFON AMIDOTI'IIO- PI-IENES DESCRIPTION OF THE PRIOR ART DESCRIPTION OF THE INVENTION The thiophenes of the invention are represented by the formula Y sow I \S R2 X (I) wherein X is fluoro, chloro or bromo; Y is hydrogen, fluoro, chloro or bromo; Z is fluoro, chloro or bromo; R is alkyl of l to 6 carbon atoms, phenyl substituted with up to 2 (O to 2) of the same or different substituents selected from fluoro, chloro, bromo or alkyl of l to 3 carbon atoms; and R is polyhaloalkyl of l to 3 carbon atoms and 2 to 7 of the same or different halogens of atomic number 9 to 35 (fluoro, chloro or bromo).

Representative alkyl R groups are methyl, ethyl, propyl, isopropyl, butyl and hexyl. Representative halophenyl, alkylphenyl or haloalkylphenyl R groups are o-fluorophenyl, m-chlorophenyl, p-bromophenyl, 2,4-

2-chloro-4-methylphenyl. Representative polyhaloalkyl R groups are difluoromethyl, trifluoromethyl, dichloromethyl, trichloromethyl, fluorodichloromethyl,

tribromoethyl, 2,2,2-trichloroethyl, l,2,2,2-tetrachloroethyl, 1,1 ,2,2-tetrabromoethyl, pentachloroethyl, 2,2,3 ,3 ,3-pentabromopropyl and 3,3 ,3-

trichloropropyl.

The preferred Y group is hydrogen, chloro or bromo. The preferred X and Z groups are chloro or bromo. The preferred R group is lower alkyl of 1 to 3 carbon atoms or phenyl. The preferred R group is trichloromethyl or tetrachloroethyl.

A preferred class of thiophenes is that represented by the formula wherein X is chloro or bromo, Z is chloro or bromo, R is methyl, ethyl, phenyl or phenyl substituted with up to 2 chloro, and R is trichloromethyl or tribromomethyl.

Another preferred class of thiophenes is that represented by the formula wherein X is chloro or bromo, Y, is chloro or bromo, Z is chloro or bromo, R is alkyl of l to 3 carbon atoms or phenyl substituted-with up to 2 of the same or different substituents selected from chloro or alkyl of l to 3 carbon atoms, and R is polyhaloalkyl of l to 2 carbon atoms and 2 to 5 of the same or different halogens selected from chloro or bromo.

The thiophenes of the invention are prepared by reacting a thienylsulfonyl chloride (II) with an amine or aniline (III) and sulfenylating the resulting sulfonamidothiophene (IV) with a polyhaloalkylsulfenyl halide (V) in the presence of an acid acceptor, as depicted in reactions (1) and (2):

som

\II X/ s z n IlCl (III) wherein X, Y, Z, R and R have the same significance as previously defined and B is an acid acceptor.

Reaction (1) is conducted by reacting substantially equimolar quantities of the thienylsulfonyl chloride (II) and the amine or aniline (III) in an inert diluent at a temperature of 0 to C. Reaction (2) is conducted by reacting substantially equimolar quantities of the sulfonamidothiophene (IV) and the sulfenyl halide (V) in the presence of an acid acceptor. Suitable acid acceptors are organic amines such as pyridine compounds, e.g., pyridine or aIpha-picoline, and lower trialkylamines, e.g., triethylamine or tripropylamine.

Generally, at least one mol of acid acceptor is employed for each mol of sulfenyl halide. The reaction is normally conducted in an inert liquid diluent, e.g., organic solvents such as chlorinated hydrocarbons. The product (I) is isolated and purified by conventional procedures such as extraction, filtration, crystallization and chromatography.

The 2,S-dihalothienylsulfonyl chlorides of formula (II) are suitably prepared by sulfonating a 2,5- dihalothiophene with chlorosulfonic acid. The 2,4,5-trihalothienylsulfonyl chloride is suitably prepared by halogenating the 2,S-dihalothienylsulfonyl chloride.

The compounds of the invention are useful for controlling fungi, particularly plant fungal infections caused by Botrytis cinerea, tomato blights caused by organisms such as Alternaria solani conidia and Phytophthora infestans conidia, powdery mildew caused by organisms such as Erysiphe polygoni and E. chicoraciarum. However, some fungicidal compounds of the invention may be more fungicidally active than others against particular fungi.

When used as fungicides, the compounds of the invention are applied in fungicidally effective amounts to fungi and/or their habitats, such as vegetative hosts and nonvegetative hosts, e. g., animal products. The amount used will, of course, depend on several factors such as the host, the type of fungus and the particular compound of the invention. As with most pesticidal compounds, the fungicides of the invention are not usually applied full strength, but are generally incorporated with conventional, biologically inert extenders or carriers normally employed for facilitating dispersion of active fungicidal compounds, recognizing that the formulation and mode of application may affect the activity of the fungicide. Thus, the fungicides of the invention may be formulated and applied as granules, as powdery dusts, as wettable powders, as emulsifiable concentrates, as solutions, or as any of several other known types of formulations, depending on the desired mode of application.

Wettable powders are in the form of finely divide particles which disperse readily in water or other dispersant. These compositions normally contain from about 5-80% fungicide, and the rest inert material, which includes dispersing agents, emulsifying agents, and wetting agents. The powder may be applied to the soil as a dry dust, or preferably as a suspension in water. Typical carriers include fullers earth, kaolin clays, silicas, and other highly absorbent, readily wettable, inorganic diluents. Typical wetting, dispersing or emulsifying agents include, for example: the aryl and alkylaryl sulfonates and their sodium salts; alkylamide sulfonates, including fatty methyl taurides; alkylaryl polyether alcohols, sulfated higher alcohols, and polyvinyl alcohols; polyethylene oxides, sulfonated animal and vegetable oils; sulfonated petroleum oils, fatty acid esters of polyhydric alcohols and the ethylene oxide addition products of such esters; and the addition products of long-chain mercaptans and ethylene oxide. Many other types of useful surface-active agents are available in commerce. The surface-active agent, when used, normally comprises from 1% to by weight of the fungicidal composition.

Dusts are freely flowing admixtures of the active fungicide with finely divided solids such as talc, natural clays, kieselguhr, pyrophyllite, chalk, diatomaceous earths, calcium phosphates, calcium and magnesiumcarbonates, sulfur, lime, flours, and other organic and inorganic solids which act as disper sants and carriers for the toxicant. These finely divided 'solids have an average particle size of less than about 50 microns. A typical dust formulation useful herein contains silica and 25% of the toxicant.

Useful liquid concentrates include the emulsifiable concentrates, which are homogeneous liquid or paste compositions which are readily dispersed in water or other dispersant, and may consist entirely of the fungicide with a liquid or solid emulsifying agent, or may also contain a liquid carrier, such as xylene, heavy aromatic naphthas, isophorone, and other nonvolatile organic solvents. For application, these concentrates are dispersed in water or other liquid carrier, and are normally applied as a spray to the area to be treated.

Other useful formulations for fungicidal applications include simple solutions of the active fungicide in a dispersant in which it is completely soluble at the desired concentration, such as acetone, alkylated naphthalenes, xylene, or other organic solvents. Granular formulations, wherein the fungicide is carried on relatively coarse particles, are of particular utility for aerial distribution or for penetration of cover-crop canopy. Pressurized sprays, typically aerosols wherein the active ingredient is dispersed in finely divided form as a result of vaporization of a low-boiling dispersant solvent carrier, such as the Freons, may also be used. All of these these techniques for formulating and applying fungicides are well known in the art.

The percentages by weight of the fungicide may vary according to the manner in which the composition is to be applied and the particular type of formulation, but in general comprise 0.5 to of the toxicant by weight of the fungicidal composition.

The fungicidal compositions may be formulated and applied with other active ingredients, including other fungicides, insecticides, nematocides, bactericides, plant growth regulators, fertilizers, etc.

EXAMPLES Example 1 Preparation of 2,5-dichloro-3-(N- methyl-N-l l ,2,2-tetrachloroethylthiosulfonamido)thiophene A 96.8 g (0.632 mol) sample of 2,5-

dichlorothiophene was added dropwise to a cooled (dry ice/acetone bath, about l0 to -l5C.) and stirred solution of 163 g (1.39 mol) of chlorosulfonic acid. After the addition was completed, the reaction mixture was stirred at 50C. for 2 hours, cooled, and then poured into 200 g of ice. The aqueous reaction mixture was extracted with methylene chloride. The methylene chloride extract was washed with saturated aqueous sodium bicarbonate solution, washed with water, dried over magnesium sulfate, and evaporated to give 87 g of 2,5-dichloro-3-thienylsulfonyl chloride.

A 10.5-g (0.34 mol) sample of methylamine in about 15 ml water was added dropwise to 43 g of the 2,5- dichloro-3-thienylsulfonyl chloride prepared above. After the addition was completed, the reaction mixture was heated at 50C. for 2 hours. The reaction mixture was then cooled, diluted with methylene chloride, washed with water, dried over magnesium. sulfate and evaporated to give 41.6 g of 2,5-dichloro-3-(N-rnethylsulfonamido)thiophene.

A 12.7-g (0.05 mol) sample of l,l,2,2-tetrachloroethylsulfenyl chloride was added slowly to a cooled (l0C.) solution of 12.5 g (0.05 mol) 2,5-dichloro-3- (N-methylsulfonamido)thiophene in 200 ml methylene S chloride. To the resulting solution was then added dropwise 5.6 g (0.55 mol) triethylamine at 5 to C. The reaction mixture was stirred at about 25C. for 2% hours, washed with water, dried over magnesium sul- Example 4 Botrytis cinerea control Compounds of the invention were tested for Botrytis cinerea control using detached, well-developed primary leaves of a 4-6 week old horsebean plant. The leaves fate and evaporated to give the product as an oil which 5 l f h crystallized from hexane as a white solid, mp were dlpped mto a 4O'ppm so i i O t 6 test 5 pound ln acetone and water containing a small amount Example 2 Preparation of 25 diChl0r0 3 (N of a nonlonlc emulsifier, then taken and place chin methyl-N-trichloromethylthiosulfonamido)thiophene a pem plate lmed Wlth two pleges O ter paper' 8 l l f t th 1 10 leaves were allowed to dry while the filter paper was A g (9055 mo S amp e O ne y amme was kept moist by adding water as required. The treated aimed dropwlse to a Soluuon 3 g leaves were then inoculated with the spores of Botrytis dlchlom'3 (Nfmethylsulfonamldo)thlop i an g cinerea fungus grown on potato dextrose agar plates. 9 mol) mchloromethylsulfenyl at 5 to The plate was covered after inoculation and kept at l mlxture was .then Smred F about 235C. The filter-paper lining of the plate was kept sat- 5 2 1 oursdwashed Wlth i dned over urated with water throughout the test. The rate of dismagnesuilm fi i an z g to e thelpmduct ease incidence was determined in 3 to 5 days, when the as 3 w w crys.ta as a w Sold disease symptoms were fully evident on non-treated 89 -91 C., when slurrled with hexane. E check leaves. The percentage disease control provided xample 3 Preparation of 2,4,5-trlchloro-3-(N-p- 20 by the test compound was calculated as the percentage tolyl-N-trichloromethylthlosulfonamldo)thiophene A disease reductlon based -on the non-treated check mlxture of 63 g (0.25 mol) 2,5-dlchlorothlen-3-yl- 1 Th t t d d th It I b sulfonyl chloride, 0.5 g sulfur monochloride and g g cgmpoun S i fi are sulfuryl chloride was heated under reflux. To the reate m a e or .companson fl methylsulfonamldo)thiophene and 5-chloro-2-(N- uxlng reaction was then added dropwise 0.5 g aluml- 25 methyl-N-trichloromethylthlosulfonamido)thiophene num trlchlorlde ln 25 g sulfuryl chlorlde. The reaction were also tested. mixture was then heated under reflux for 3 hours, cooled, diluted with 400 ml cold water and extracted Example 5 Tomato Late Blight with methylene chlon de' The methylene chlonde Compounds of the invention were tested for the contracts washed wlth water saturaPed aqueous trol of the Tomato Late Blight organism Phylophthora f blcarbomftei dned over magnesufm Sulfa? and infestans conidia. Fiveto six-week-old tomato (variety pp t0 glve g of zifiis'mchlorothlen'} Bonny Best) seedlings were used. The tomato plants y fi y Chloride, Whlch Crystanlzed from hexane as were sprayed with a 250-ppm solution of the test com- 3 50nd, 55 pound in acetone, water, and a small amount of a non- A Solution of 21.4 g l) P- methyl ionic emulsifier. The sprayed plants were then inocuene chlol'lde was addfid PY to a sohmon of 8- lated one day later with the organism, placed in an eng H101) 2,4,5fiflchlofothlen'3-ylsulfonyl Chloflde vironmental chamber and incubated at 6668F. and m methylene chlorlde ml total) at about 100% relative humidity for at least 16 hours. Following feactlon. nlllxtufe was anPWed to f to about the incubation, the plants were allowed to dry and then 25 C. with stirring and then stirred at 25 C. for 1 hour. 40 were maintained at 6 3()% l i h idi f The reaction was filtered and the filtrate Was Washed proximately 7 days The percent diseas control prowith water, dried over magnesium sulfate and evapoid d b a given test compound was b d on h rated F 30 g of i -P' y cent relative reduction relativee to untreated check fonamldofihlophenei -P- IMO-125C plants. The test compounds and the results are tabu- A 30-g (0.03 mol) sample of triethylamine was added d i T bl I][ dropwise to a solution of 80 g (0.022 mol) 2,4,5- trichloro-3-(N-p-tolylsulfonylamido)thiophene and 4.2 Exam le 6 Tomato Early Blight g tfichlofomethylsulfenyl Chloride in 150 Compounds of the invention were tested for the conml methylene chloride at l0C. The reaction mixture trol of the Tomato Early Blight organism, Alternaria was allowed to warm to about 25C. and then stirred at sclani conidia. Tomato (variety Bonny Best) seedlings about 25C. for 1 hour. The reaction mixture was of 6 to 7 weeks old were used. The tomato plants were washed with water, dried over magnesium sulfate and sprayed with 250-ppm solution of the test compound in stripped to give the 2,4,5-trichloro-3-(N-p-tolyl-N- an acetone-and-water solution containing a small trichloromethylthiosulfonamido)thiophene product, as amount of non-ionic emulsifiers. The sprayed plants an oil which crystallized from ether-hexane as a White were inoculated one day later with the organism, dried solid, m.p. 1 1 l-l 12C. and maintained at -80% relative humidity for about Other compounds of the invention were prepared by 12 days. Percent disease control was based on the perthe procedures of Examples 1-3. These compounds cent disease development on untreated check plants. and the compounds of Examples l3 are tabulated in The compounds tested and the results are tabulated in Table I. 60 Table IV.

TABLE I Melting Elemental Analysis Point Sulfur Chlorine Compound C. Calc. Found Calc. Found 2,5-dichloro3-( Nmethyl-N- l l ,2,Z-tetrachloroethylthiosulfonamido )thiophene -86 21.7 19.4 47.9 45.5 2,5-dichloro-3-(N-methyl-N-trichloromethylthiosulfonamido)- thiophene 89-91 24.3 24.5 44.8 43.4

TABLE I Continued Melting Elemental Analysis Point Sulfur Chlorine Compound C. Calc. Found Calc. Found 2.4,5-trichloro-3-(N-p-tolyl-N-trichloromethylthiosulfonamido)- thiophene 111-112 19.0 19.0 42.0 40.9 2,5-dichloro-3-(N-phenylN-1,1,2,2-tetrachloroethylthiosulfonamido)thiophcnc 170-173 19.0 18.9 42.0 41.1 2,5-dichloro-3-(N-phcnyl-N-trichloromethylthiosulfonamido)- thiophenc 110-112 21.0 20.7 38.7 38.6 2,5-dichloro-3-(N-p-ch|orophenyl-N-trichloromcthylthiosulfonamido)thiophene 94-95 19.6 18.6 43.2 40.6 2,5-dichloro-3-( N-isopropyl-N-trichloromethylthiosulfonamido thiophcne 56-57 22.7 21.6 41.8 39.7 2.5-dichloro-3-(N-ethyl-N-trich1oromethylthiosulfonamido)- thiophcne 54-55 23.5 23.3 43.3 41.8 2,5-dichloro-3-(N-p-tolyl-N-trichloromethylthiosulfonamido)- iophene 86-87 20.4 20.1 37.6 37.1 2,5-dichloro-3-(N-3,5-dich|oropheny1-N-trichloromethylthiosulfonamido)thiophene 111-113 18.3 17.7 47.1 51.4 2,5-dichloro-3-(N-Z.6-dimethylphenyl-N-trichloromethylthi0- sulfonamido)thiophenc 121-122 19.8 19.0 36.5 35.0 2.4,5-trich1oro-3-(N-p-tolyl-N-l,1,2,Z-tetrachloroethylthiosulfonamido)thiophene 132-133 17.3 17.6 44.8 43.6

TABLE I1 Botrytis cinerea Control Compound Control 2,5-dichloro-3-(N-methy1-N-trich1oromethylthiosulfonamido)thiophene 56 2,5-dichloro-3-(N-ethyl-N-trich1oromethylthicsulfonamido )thiophene 27 2,5-dichloro-3-(N-phenyl-N-trichloromethylthiosulfonamido)thiophene 79 2,5-dich1oro-3-(N-p-chlorophenyl-N-trichloromethylthiosulfonamido)thiophene 44 2,4,5-trich1oro-3-(N-p-to1y1-N-trichloromethylthiosulfonamido)thiophcne 73 2.4,5-trichloro-3-(N-p-tolyl-N-1 .1,2,Z-tetrachloroethylthiosulfonamido)thiophene 33 2,5-dichloro-3-(N-methylsulfonamido)thiophene -chloro-2-(N-methy1-N-trich1oromethylthro(sulfonamido)thiophene 0 TABLE 111 Tomato Late Blight Control 2,5-dichloro-3-(N-methyl-N-1,1,2,2-tetrachloroethylthiosulfonamido)thiophene 44 2,5-dich1oro-3-(N-methyl-N-trichloromethylthiosulfonamido)thiophene 63 2,5-dichloro-3-(N-isopro y1-N-trich1oromethylthiosulfonamido)thiophene 71 2,4.5-trichloro-3-(N-p-to yl-N-l ,1 ,2,2-tetrach1oroeth lthiosulfonamido)thiophene 34 2,4,5-trichloro-3-(N-p-to1yl-N-trichloromethy1thiosu fonamido)thiophene 34 TABLE IV Tomato Early Blight Control 2,5-dichloro-3-(N-phenyl-N-trichloromethylthiosulfonamido)thiophene 93 2.5-dich1oro-3-(N-p-chlorgrhenyLN-trichlorometh lthiosulfonamido)thiophene 71 2,5-dichloro-3-(N-p-tolyl- -trichloromethylthiosul onamido)thiophene 81 2,5-dichloro-3-(N-2,6-dimeth lpheny1-N-trich1oromethylthiosulfonamido)thiophene 96 2,5-dichloro-3-(N-isopro yl- -trichloromethylthiosulfonamido)thiophene 80 2.4.5-trich1oro-3-( N-p-to yl-N- 1 ,1,2,2-tetruchloroethylthiosulfonamido )thiophene 27 27 2,4,5-trichlo ro-3-( N-p-tolyl-N-trich1oromethylthiosulfonamido)thiophene What is claimed is: 1. A compound of the formula X S Z wherein X is fluoro, chloro or bromo, Y is hydrogen, fluoro, chloro or bromo, Z is fluoro, chloro or bromo, R is alkyl of l to 6 carbon atoms, phenyl or phenyl substituted with up to 2 of the same or different substituents selected from the group consisting of fluoro, chloro, bromo and alkyl of 1 to 3 carbon atoms, and R is polyhaloalkyl of l to 3 carbon atoms and 2 to 7 of the same or different halogens selected from the group consisting of fluoro, chloro and bromo.

2. The compound of claim 1 wherein Y is hydrogen and X and Z are the same halogen and are chloro or bromo.

3. The compound of claim 1 wherein Y is chloro or bromo and X, Y and Z are the same halogen.

4. The compound of claim 1 wherein R is polyheloalkyl of 1 to 2 carbon atoms and 2 to 5 of the same or different halogens selected from chloro or bromo.

5. The compound of claim 4 wherein R is trichloromethyl or tetrachloroethyl.

6. A compound of the formula R1 H 50 m:

sccl

X S Z y SO N X S Z 9 10 wherein X is chloro or bromo, Y is chloro or bromo, Z rabromoethyl. is chloro r bromo, R is alkyl of 1 to 3 carbon atoms z,4,5 trichloro 3 (N phenyl N or phenyl substituted with up to 2 of the same or different substituents selected from the group consisting of chloro and alkyl of 1 to 3 carbon atoms and R is tri- 5 to Clam chloromethyl, tribromomethyl, tetrachloroethyl or tettrichloromethylthiosulfonamido)thiophene, according 

1. A COMPOUND OF THE FORMULA
 2. The compound of claim 1 wherein Y is hydrogen and X and Z are the same halogen and are chloro or bromo.
 3. The compound of claim 1 wherein Y is chloro or bromo and X, Y and Z are the same halogen.
 4. The compound of claim 1 wherein R2 is polyhaloalkyl of 1 to 2 carbon atoms and 2 to 5 of the same or different halogens selected from chloro or bromo.
 5. The compound of claim 4 wherein R2 is trichloromethyl or tetrachloroethyl.
 6. A compound of the formula
 7. 2,5-dichloro-3-(N-methyl-N-trichloromethylthiosulfonamido)thiophene according to claim
 6. 8. 2,5-dichloro-3-(N-phenyl-N-trichloromethylthiosulfonamido)thiophene according to claim
 6. 9. A compound of the formula
 10. 2,4,5-trichloro-3-(N-phenyl-N-trichloromethylthiosulfonamido)thiophene, according to claim
 9. 